Calabrese, J.R. et al. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am. J. Psychiatry 156, 1019−1023

Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 08/1999; 156(7):1019-23.
Source: PubMed


New mood stabilizers are needed that possess efficacy for all phases of bipolar disorder. This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy.
A 48-week, open-label, prospective trial was conducted in 75 patients with bipolar I or bipolar II disorder. Lamotrigine was used as adjunctive therapy (N = 60) or monotherapy (N = 15) in patients presenting in depressed, hypomanic, manic, or mixed states.
Of the 40 depressed patients included in the efficacy analysis, 48% exhibited a marked response and 20% a moderate response as measured by reductions in 17-item Hamilton Depression Rating Scale scores. Of the 31 with a hypomanic, manic, or mixed state, 81% displayed a marked response and 3% a moderate response on the Mania Rating Scale. From baseline to endpoint, the depressed patients exhibited a 42% decrease in Hamilton depression scale scores, and the patients presenting with hypomania, mania, or a mixed state exhibited a 74% decrease in Mania Rating Scale scores. The most common drug-related adverse events were dizziness, tremor, somnolence, headache, nausea, and rash. Rash was the most common adverse event resulting in drug discontinuation (9% of patients); one patient developed a serious rash and required hospitalization.
These open-label data provide preliminary evidence that lamotrigine may be an effective treatment option for patients with refractory bipolar disorder; however, potential benefits must be weighed against potential side effects, including rash.

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    • "Epi RCTs 14–77 347 With VPA 28 48/69 16w 96 mg/d 117 20 With CBZ 31 61/68 16w 347 mg/d 129 9 With PHT 33 45/50 16w 359 mg/d 95 0 Farrell et al. (1996) [34] Canada Epi Open-label Children 56 With VPA 24 M 21 4 Without VPA 24 M 35 1 Calabrease et al. (1999) [35] USA Bipolar Open-label Adults 75 With VPA 48 W 15 1 LTG alone 48 W 60 6 Beghi et al. (2003) [36] "
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    ABSTRACT: We systematically reviewed studies to provide current evidence on the incidence and risk of skin rash in patients with LTG therapy. PubMed and Scopus databases, up to 15 March 2014 were searched to identify relevant studies. Eligible studies included prospective studies, retrospective studies and postmarketing reports, which included data of skin rash in patients with LTG therapy. Forty-one articles met the entry criteria. A total of 4447 patients with LTG therapy from 26 prospective studies, 2977 patients from 8 retrospective studies, and 26,126 patients from 5/7 postmarketing reports were included. The overall incidence of skin rash with LTG therapy was 9.98% (444/4447) from prospective studies, 7.19% (214/2977) from retrospective studies, and 2.09% (547/26,126) from postmarketing reports. A meta-analysis of the risk of skin rash in 21 prospective studies, did not show a significant difference between patients with LTG and other drugs, including placebo, other ADEs or lithium (OR 0.99-2.41). In 6 respective studies, there was a significantly higher OR in patients with LTG compared with those with non-aromatic AEDs. However, there was no significant difference in rash risk between patients with LTG and aromatic AEDs. Our study showed that LTG significantly increased the risk of developing a skin rash compared to non-aromatic AEDs. Our results support the need for large prospective population-based studies and clinical trials to determine whether LTG increases the risk of developing a skin rash than compared to other drugs. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
    Seizure 02/2015; 25:52-61. DOI:10.1016/j.seizure.2014.12.001 · 1.82 Impact Factor
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    • "the number needed to treat is relatively high ( Popovic et al . , 2011 ) . Nonetheless , the effectiveness of lamotrigine in acute treatment is vigorously debated . On one hand , some studies have shown the usefulness of this agent in acute treatment of bipolar depression , even in refractory and in rapid cycling patients ( Bowden et al . , 1999 ; Calabrese et al . , 1999a , 1999b ; Frye et al . , 2000 ; Vieta et al . , 2010a ) . On the other hand , benefits compared to placebo have been shown only in one of the five clinical - trials sponsored by the industry when reported sepa - rately ( Calabrese et al . , 2008 ) and in an adjunctive trial ( van der Loos et al . , 2009 ) . Nevertheless , an independent"
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    ABSTRACT: BACKGROUND: The use of lamotrigine is a point of discrepancy among the diverse guidelines published on the management of bipolar disorder (BD). Evidence supporting the long-term efficacy is reasonably robust. Nonetheless, the effectiveness of lamotrigine in acute treatment is vigorously debated and it is unclear how this drug is used in routine clinical practice. This subanalysis of the SIN-DEPRES study was designed to understand the clinical profile of bipolar patients receiving lamotrigine. METHODS: In this prospective national multicenter study, 652 patients with clinically stable bipolar I and II disorder were recruited. Clinical assessments included sociodemographic and clinical data, the Modified Clinical Global Impression scale for BD (CGI-BP-M), the Hamilton Depression Rating Scale (HDRS), and prescriptions of psychotropic medications and their doses. RESULTS: By means of a logistic regression model, an association between receiving treatment with lamotrigine and the following clinical variables was found: number of past depressive episodes (O.R.=2.875, 95% CI: 1.203-6.869, p=0.018), depressive polarity of the most recent episode (O.R.=1.945, 95% CI: 1.267-2.985, p=0.002), severity in CGI-BD-M depression (O.R.=1.850, 95% CI: 1.215-2.817, p=0.004), bipolar II disorder diagnosis (O.R.=1.635, 95% CI: 1.078-2.482, p=0.021) and number of episodes per year (O.R.=1.310, 95% CI: 1.069-1.605, p=0.009). LIMITATIONS: Subanalysis of the SIN-DEPRES study with a cross-sectional design. CONCLUSIONS: The use of lamotrigine in clinical practice is in accordance with most of the guidelines, which support its use in patients with depressive predominant polarity and bipolar II disorder.
    Journal of Affective Disorders 07/2012; 143(1-3). DOI:10.1016/j.jad.2012.05.035 · 3.38 Impact Factor
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    • "Building on anecdotal reports of lamotrigine's psychotropic properties in epileptic and bipolar patients, Calabrese et al (Calabrese, Bowden, McElroy, et al 1999) conducted the fi rst study to investigate its spectrum of therapeutic activity in bipolar disorder. This 48-week, open-label, prospective trial used lamotrigine as monotherapy or adjunctive pharmacotherapy in 75 patients with refractory bipolar I or II disorder, who variously presented in depressed, hypomanic, manic or mixed phases of the illness. "
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    ABSTRACT: Lamotrigine has emerged with a distinct place in the pharmacological treatment of bipolar disorder, with the potential to treat and prevent bipolar depression, which is the dominant and arguably most disabling and under-treated phase of the illness. This review examines the published clinical trials of lamotrigine in bipolar treatment. While the data supports its tolerability and safety, the strongest evidence for its efficacy lies in the prevention of bipolar depression, with weaker evidence for the treatment of acute bipolar depression, refractory unipolar and bipolar depression, and rapid cycling bipolar disorder. The total number of published well designed trials is small, even the maintenance evidence is derived from two studies. However, this relative inadequacy compares favorably with the alternative treatment options for bipolar depression, which are marked by poor efficacy or risk of polarity switch. The designation of lamotrigine as first-line treatment for bipolar depression prophylaxis should be done in cognizance of this context, and it would seem prudent to await greater evidence of efficacy before designating lamotrigine as first-line treatment for other bipolar indications. Further randomized controlled trials are required to consolidate the available findings and to explore the boundaries of lamotrigine's efficacy, which may encompass the soft spectral disorders.
    Neuropsychiatric Disease and Treatment 09/2007; 3(4):463-74. · 1.74 Impact Factor
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